Morpholine compounds



compounds.

Patented Apr. 24, 1945 UNITED STATES PATENT FFlCE- MORPHOLINE COMPOUNDS Joseph B. Dickey and James G. McNaiiy, Rochester, N. Y., assignors to Eastman Kodak Com- Y. a corporation of New pany, Rochester, N.

Jersey No Drawing. Application November 16, 1940,

Serial No. 365,989

7 Claims. (01. 260-244) This invention relates to certain new morpholine compounds and particularly new morpholine compounds which contain a, benzoor naphthoring and certain other groupings inaddltion to the morpholine nucleus, and which are particularly useful as dye intermediates.

Morpholine compounds are known industrially, and as indicated, are useful for dye intermediates. The use of certain morpholine compounds in the production of dyes is described in our copending application, Serial No. 309,688 filed December 16, 1939, now Patent No. 2,251,947, dated August 12, 1941. We have now found additional new morpholine compounds and methods of manufacture,

which compounds extend the field of usefulness of morpholine compounds and represent a substantial improvement over many of the morpholine compounds heretofore available. I

This invention has for one object to provide new morpholine compounds and in particular morpholine compounds containing a benzoor naphtho-group in addition to, or in conjunction with, the morpholine nucleus and certain substious benzoand naphthomorpholine with reagents such as alkylene oxides and chlorohydrins, halogenated acids, acid amides, ethers, ketones, esters and the like, unsaturated aliphatic acid nitri-les and the like. In general the structure of thenew compounds may be representedby formulas as follows: 1

where X is oxygen or sulfur; R is a substituted alkyl group; n is '0, 1, etc.; Z is a monovalent substituent. However, it should be noted in this respect that the monovalent substituent will probably comprise alkyl, alkoxy, halogen, and NaSOa and the like, usually in some position other than the sixth position. For example, a simple amino group in the sixth position yields a product which will not couple in azo dye manufacture. Q is a radical of the group selected from hydrogen alkyl, cycloalkyl, aryl or heterocyclic.

The morpholin compounds which are used as starting materials in the production of our novel morpholine derivatives may be obtained from any convenientsource or produced by known processes. For example, methods of producing certain morpholine compounds are described in Berichte.

Or the starting morpholine compounds may be obtained by the methods described, or referred to, in our copending application 309,688 (see above) or the copending companion application in the name of Strain andDickey, Serial No.

365,988, filed November 16, 1940, entitled Process for producing morpholine compounds.

A more complete understanding of our inven- 'tion will be had from the consideration of the following examples which'show the production of various of our new morpholine compounds by procedure illustrating one type v of method for their preparation. While the following examples illustrate the preferred embodiments of our invention, they are not tobe considered an undue limitationupon our invention.

Exmna 1 N-p-hudrozcuethpl d-methulbenzomorpholine One gram mole of 3-methyl benzomorpholine is heated in an autoclave at 160-200 with 1.25

gram moles of ethylene oxide for 6-8 hours.

When cool the reaction products are removed and distilled under reduced pressure. There is obtained an excellent yield of N-p-hydroxyethyl- 3-methylbenzomorpholine boiling at 145-148/3 mm. Similarly,-we have prepared N-p-hydroxyethylbenzomorpholine, N-p-hydroxyethylbenzothiomorpholine, N-p-hydroxyethyl-3,5-dimethyl- 5 pholine, etc.

benzomorpholine, N-p-hydroxyethyb'i-methylmorpholine, N-p-hydroxyethyl-a-naphthomor- EXAMPLE 2 2,-3.5-trimethyl-N-Z,3-dihydro:ruzirom lbenzothiomcrpholtne One gram mole 2,8,5-trimethy1ben2othiomor phoiine is heated in an autoclave with glycidol at -150 for 4-12 hours., The product on distillation gives agood yield of the N-2,3-dlhydro:wpropyl compound boiling at 198-20173 mm. Similarly, the following have been prepared: 2-psulfophenyl-N-2,3-dihydroxypropylbenzothiomorpholine, 2-sulfobenzyl-N-2,3-dihydroxypropyl-anaphthoquinoline-7-sulfonic acid, 2,3-diethyl-N- 2,3 dihydroxypropylbenzomorpholine acid-7, etc.

sulfonic EXAMPLE 3 Two gram moles benzomorphollne are heated with one gram mole of 1,3-butylene oxide at 160 200 for 4-10 hours. The reaction product has one mole 3-ethyl-7-methylbensomorpholino is 4-12 hours the reaction product is distilled. There is 7 obtained 3-ethyl-7-methyl-benzo-N-p-propionitrile boiling at 195-200/3 mm. Similarly, there have been prepared: 7-hydroxy-2-methylbenzo- 5 thiomorpholine ,6 methyl p -proplonitrile, etc. the formula Under suitable conditions these nitriles can be g hydrolyzed to the acid, amide or ester and with 0 g o a catalyst such as Raney nickel reduced to com- C pounds having the formula:

N--CHiOHOE-CHOHOHQ N l0 IFCHPCHPCHPNHB Hi Similarly, there have been prepared: O l6 GHQ -oH etc. 80am SONB From the foregoing it can be seen that we have C c provided methods for producing our new compounds, which methods are relatively uncompli- N--Q oHoHCH \N 2o ated andconvenient and give. excellent yields.

Our methods may generally be described as reaacting under conditions of heating in an auto- EXAMPLE 4 clave, the benzoor naphthomorpholine starting am materials with a reagent which reacts at the N dmydmwpmwz 2 metmlbenz Mane nitrogen atom of the morpholine nucleus to cause One m 3-methvlbenzomorpholine is heated the addition of the desired 'substituent at this to 140 in a a mechanical stiner. point AS described alkylene oxides chlorohy- To th are added moles sodium bicarbonate drins or other halogen derivatives as halogenated and then 1251110165 glycerolchlorohydrin are addesters or ethers or nitr11es may be used as the ed slowly. After the chlorohydrln is added heatreagent. It will be observed, however, that we mg and Stirring are continued until no more generally employ a halogenated derivative of a hen dioxide is evolved. The product is then separadical having a rather long chain, while we do rated f the salt by means alcohol and not wish to be bound by any theory respecting our tilled under reduced pressure There 18 Obtained invention, it may be that to some extent the addia 8 yield of N-2,3-d1hyd 0 yI 0Dy tion of these long-chain compounds with solumorpholine melting at from benzenebilizing groups contribute to the quality of our Simil rly, t f llo h v n P p r new compounds, rendering them useful as dye in- N dihydroxypropylm termediate in azo dye manufacture. pholine, N-2,3-dihydroxypropyl- -dim thy As indicated, our new compounds are partico p e, N dihydroxypropy ularly usefulein dye manufacture, producing for benzyl--11aphth0m0rph0line, -flexample, in someinstances, bluer dyes than herebenzo o p o i e. N fl h droxynro r tofore obtainable. In addition they have the xymethyl 5 methoxybenzomorpholin -r property of easily coupling in azo dye manufachydroxypropyl 2 methoxymethyl n m ture. Also, .our new compounds are useful in line. tfiother fields. For example, certain of our com- EXAM? 5 pounds may have value under some conditions as a-Naphthothiomorpholine-N-acetamide antiofldantsreducing agents-and the likev From he foregoing it is therefore apparent one mole e-naphthothwmomhollne is heated that our invention is susceptible to some modifica- 130 in ethaml with .1 meal" tion; hence, we do not wish to be restricted exbonate and 1 mole chloroacetamide. when no ceptmg ins far as is necessitated by the an more carbon dioxide is evolved, the salt is filtered and the spirit f the appended mama out and the product allowed to crystalgze Shtlfiwe claim: larly, the following have been prepare -nie 1 The compounds which are represented by ylbenzomorpholine acetamide, 2-methyl-5-metha member selectedfmm the grbup consisting of oxybenzomorphollne-N-p-propionamide, etc. the mubwmg formulas:

Exmu 6 N-carbon/methul-5-methvl-7-methozybenzo- I morpholine sodium salt '0 0-4} One mole S-methyl-l-methoxybenzomorphclinc (J-Q is heated in water with one mole sodium chlcrox acetate at 50. The excess morpholine is removed by steam'and the compound is recovered by evaporation. Similarly, the following have been prepared: N p carboxyethyl-2-methyl-5-carboxybenzomorpholine, N-CHz-CHa-CHz-COOK-7-sulfobenzomorpholine, etc.

Exmu 7 to 3-ethyl-7-methulbenzomorpholme-N-ppmpionimle wherein R represents a hydroxyalkyl group, Q represents a member selected from the group consitting of hydrocen and alkyl groups at least heated in an autoclave with one mole aerylonitrile. at temperatures ranging between 50-250. After 76 one Q on each carbon stern being hydrogen. 1: represents a member selected fro the group con- 1 sisting of oxygen and sulfur an Z represents a. member selected from the group consisting oi laydrogen. alkyl groups, alkoxyl groups and halogen. 5

2; The compounds which are represented by' the following formula:

A De wherein It represents a hydroxyalkyl group, Q represents a member selected from the group consisting of hydrogen and alkyl groups at least one Q on each carbon atom being hydrogen, X represents a. member selected from the group consisting of oxygen and sulfur and Z represents a member selected from the group consisting of hydrogen, alkyl groups, allroxyl groups and halogen.

8. The compounds which are represented by the following general formula:

wherein R represents a hydroxyaikyl group, Q 35 methylbennomorpholine.

represents a member selected from the group eonsistingo'i hydrogen and alkyl groups at least one Q on each carbon atom being hydrogen. 1! represents a member selected from the group consisting of oxygen and sulfur and Z represents a member selected from the group consisting of hydro- .gen, slkyl groups; elkoxyl groups and halogen.

4. The compounds which are represented by the iollowing general formula:

N Q e q wherein It represents a hydroxralkyl group. Q represents a member selected from the group consisting of hydrogen andalkyl groups, at least one Q on each carbon atom being hydrogen and Z represents a member selected from the group consisting of hydrogen, alkyl groups, sikoxyl groups and halogen.

5. Compounds having the general lormulaz' en. err-cm N/ g om-cnom-cmon 30 mm at least one 2 is alkyl and any remainin! Z ishydrogent 8. The compound 2,7-dimethyl-N-2.3-dihy'- droxypropi'lbennomorpholine.

7. The compound N-2,3-di hydroxypropyl-2- sosnrn a; mom. r slums G. McNALLY. 

